DESCRIPTION (provided by Dr. Whittaker): Cornell University shall perform a detailed study of the role of the hemagglutinin (HA) molecule in establishment of avian influenza viruses in a mammalian host, focusing on those events that control fusion activation of the HA, a critical step for influenza virus replication. To accomplish this goal, Dr. Whittaker and his research team will: a) Characterize influenza HA resistance to the low pH environment of the avian gastrointestinal tract; b) Determine the role of the conserved patch of basic amino acids present on the HA of many avian influenza viruses and also on the H1 HA of the 1918 virus in host adaptation. These studies shall determine the relationship of the basic patch to fusion activation, focusing on avian and human H1 viruses; and c) Determine the molecular basis for the establishment of high pathogenicity avian influenza viruses in a mammalian population by carrying out structure-function determinations of the H7 HA. These experiments shall focus on how the unique insert at the cleavage site of the H7 virus controls viral pathogenesis in a mammalian host.